Clinical Utility of a Targeted Next-Generation Sequencing Panel for Inherited Platelet Disorders in Children
Diagnostics, cilt.15, sa.17, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 15 Sayı: 17
- Basım Tarihi: 2025
- Doi Numarası: 10.3390/diagnostics15172210
- Dergi Adı: Diagnostics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals
- Anahtar Kelimeler: genetic diagnosis, inherited platelet disorders, next-generation sequencing, pediatric patients, thrombocytopenia
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Background/Objectives: Inherited platelet disorders (IPDs) are diverse conditions characterized by abnormalities in platelet count and function. Next-Generation Sequencing (NGS) shows promise as a diagnostic tool in the diagnosis of IPDs. This study aims to assess the clinical value and limitations of using a targeted NGS panel in diagnosing children with suspected IPDs. Methods: We conducted a retrospective study of 93 children evaluated for suspected IPDs. A targeted NGS panel of 14 IPD-associated genes (RUNX1, WAS, ADAMTS13, ANKRD26, CYCS, GATA1, GP1BA, GB1BB, GP9, ITGA2B, ITGB3, MASTL, MPL, MYH9) was performed. Results: Genetic variants were identified in 30 patients (32.3% of the cohort). A total of 37 variants, of which 15 (40.5%) were novel, were found across 11 of the 14 genes on the panel (all except MPL, CYCS, and RUNX1). Variants were most frequently found in ITGB3 (18.9% of variants), GP1BA (16.2%), and ADAMTS13 (16.2%) genes. The majority of variants (64.9%) were classified as variants of uncertain significance (VUS), followed by likely pathogenic (LP) (27%) and pathogenic (8.1%) variants. Most variants were in a heterozygous state (73%). Specific cases highlighted complex genetic scenarios, such as co-occurring variants, and the identification of pathogenic and LP variants in patients initially presenting with immune thrombocytopenia. Conclusions: NGS helps to identify genetic causes, assess risk, manage, and provide genetic counseling in the management of IPDs. However, the prevalence of VUS underscores the need for a multidisciplinary approach to evaluate NGS results accurately.